Use of a bovine model to study the role of adhesion molecule CD11/CD18 in hemodialysis-induced neutropenia

被引:5
作者
Rabb, H
Chandran, PKG
Arnaout, MA
Kehrli, ME
机构
[1] Johns Hopkins Univ Hosp, Div Nephrol, Baltimore, MD 21205 USA
[2] Nephrol Clin, Des Moines, IA USA
[3] USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA
[4] Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA
[5] Harvard Univ, Sch Med, Boston, MA USA
关键词
hemodialysis (HD); integrins; leukocyte adhesion; neutropenia; cows;
D O I
10.1053/ajkd.2002.31416
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
The early neutropenia that occurs with cellulose-based dialysis membranes is believed to result from a cascade of immune events: complement activation, engagement of leukocyte adhesion molecules, cytokine release, and leukocyte sequestration. The beta(2) integrin CR3 (CD11b/CD18) is upregulated during hemodialysis, binds complement factor iC3b, and mediates leukocyte adhesion to endothelium and leukoaggregation. Despite being invoked in dialysis-induced neutropenia, there is no direct evidence of a role for CD11b/CD18 in the neutropenla. A unique animal model of beta(2)-integrin deficiency was discovered in calves experiencing recurrent infections and a paucity of leukocytes in infected tissue. We hypothesized that beta(2) integrins mediate the neutropenia of dialysis and directly tested this hypothesis using beta(2)-integrin-deficient calves. Two 3-month old beta(2)-integrin-deficient and two age-matched Holstein calves were dialyzed using cuprophane dialyzers. beta(2)-integrin-deficient calves had less than 2% of normal neutrophil CD18 expression by flow cytometry. Normal calves had a marked decrease in circulating neutrophils (P < 0.05) to 15% of normal 15 minutes into dialysis (total, four treatments), as well as a decrease in monocytes to 39% (P < 0.05) and lymphocytes to 58% (P < 0.05). CD18-deficient calves had an attenuated decrease in neutrophils (65%; P = not significant), monocytes (78%; P = not significant), and lymphocytes (105%; P = not significant) at 15 minutes. These data, although obtained in a small sample, show that a bovine model can be used to study the early neutropenia of dialysis. These data also suggest that a direct role of beta(2) integrins may be occurring in this process. (C) 2002 by the National Kidney Foundation, Inc.
引用
收藏
页码:587 / 593
页数:7
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